Estradiol receptors mediate estradiol-induced inhibition of mitochondrialCa2+ efflux in rat caudate nucleus and brain stem

Our earlier studies found that in vitro estradiol modulates mitochondrial Ca2+ transport in discrete brain regions. The present study examined the role of estradiol receptors (ERs) in estradiol-induced inhibition of Ca2+ efflux from synaptosomal mitochondria isolated from rat caudate nuclei and brain stems. Radioactively labeled CaCl2 (0.6–0.75 μCi 45CaCl2) was used for Ca2+ transport monitoring. The results revealed that in the presence of ER antagonist 7α,17β-[9[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estra- 1,3,5(10)-triene-3,17-diol (ICI 182,780) (1 μmol/L), the inhibitory effect of estradiol on mitochondrial Ca2+ efflux was more than 60% decreased, suggesting the involvement of ER in this mode of estradiol neuromodulatory action. When particular contributions of ERα and ERβ were tested, it was found that ERβ agonist 2,3-bis(4-hydroxy phenyl)-propionitrile (10 nmol/L) inhibited Ca2+ efflux more than 20%, while the inhibition with ERα agonist 4,4’,4’’-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (10 nmol/L) was about 10%, both compared to the control. Both agonists demonstrated attenuation of Ca2+ efflux decrease in the presence of mitochondrial Na+/Ca2+ exchanger antagonist 7-chloro-5-(2-chlorophenyl)-1,5-dihyhdro-4,1-benzothiazepin-2(3H)-one (10 μmol/L), showing interference with the inhibitory action of that agent. Our results strongly indicate ERs as the mediators of estradiol-induced mitochondrial Ca2+ efflux inhibition in rat caudate nucleus and brain stem synaptosomes.